NCT06106906招募中1 期
A Single-center Clinical Study Evaluating the Safety and Efficacy of CD19 CAR-T in Active Systemic Lupus Erythematosus
Wuhan Union Hospital, China1 个研究点 分布在 1 个国家目标入组 15 人开始时间: 2024年6月19日最近更新:
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Safety and tolerability
研究概览
简要总结
The purpose of the study is to explore the safety and efficacy of CD19 CAR-T in active systemic lupus erythematosus.
详细描述
The prognosis of patients with active systemic lupus erythematosus (SLE) remains poor, due to two major therapeutic obstacles: (1) current treatment strategies including glucocorticoids, immunosuppressive agents, biological agents, are still difficult to achieve disease control, making the disease condition of some patients continue to be active or even worse; (2) some patients are unable to wean themselves off glucocorticoid and face the risk of numerous adverse effects caused by long-term glucocorticoid dependence, such as glucocorticoid-related diabetes, femoral head necrosis, hypertension, stress ulcers, and infection, etc. Therefore, there is a strong unmet clinical need for more effective treatment for patients suffering from active SLE. Several preclinical studies have shown the efficacy of CAR-T cell treatment in SLE. The aim of this study is to investigate the safety, tolerability, preliminary efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of CD19 CAR-T cell therapy in active SLE. Patients with active SLE will be invited to participate in the study, to receive CD19 CAR-T intravenous infusion and follow-up visits of up to 2 years after enrollment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants or their guardians understand and voluntarily sign the informed consent form, and be able to complete all the documents, procedures, follow-up examinations and treatments specified in the study protocol, with good compliance;
- •Age range from 18 to 70 years old, regardless of gender;
- •Body weight ≥ 40kg;
- •Participants diagnosed with SLE according to the American College of Rheumatology (ACR) 1997 revised criteria for SLE at least 24 weeks prior to signing the informed consent form;
- •Active SLE needs to meet the following criteria at screening:
- •SELENA-SLEDAI score ≥ 6 points; PGA ≥ 1 points;
- •Have received at least 8 weeks of standardized treatment for SLE prior to screening;
- •Female participants need to have a negative pregnancy test, and participants agree to take effective contraceptive measures throughout the study.
排除标准
- •Known hypersensitivity to prednisone, immunosuppressive agents;
- •Diagnosis of active severe lupus nephritis within 8 weeks prior to screening, requiring medications prohibited by the research protocol for active nephritis, hemodialysis or prednisone ≥ 100 mg/d, or equivalent glucocorticoid therapy for ≥14 days;
- •Suicidal ideation within the past 6 months based on assessment by Columbia-Suicide Severity Rating Scale (C-SSRS) at screening; or any suicidal behaviors within the past 12 months or recurrent suicidal behaviors during the subject's lifetime;
- •Presence of SLE or non-SLE related central nervous system diseases or pathological changes within 8 weeks prior to screening;
- •Existence of other lupus crisis within 8 weeks prior to screening;
- •Previous or current diagnosis of non-SLE-related inflammatory arthropathy or skin diseases;
- •Previous or current diagnosis of severe vasculitis due to other diseases excluding SLE;
- •History of vital organ transplantation or hematopoietic stem cell/or bone marrow transplantation;
- •Have received plasmapheresis, hemodialysis, intravenous immunoglobulin within 14 days prior to screening;
- •Other autoimmune diseases requiring systemic therapy;
- •Subjects with active viral hepatitis B; Subjects with positive hepatitis C virus (HCV) antibodies; Subjects with positive human immunodeficiency virus (HIV) antibodies; Sujects with positive extracellular DNA quantification of cytomegalovirus (CMV); Sujects with positive extracellular DNA quantification of EB virus (EBV);Subjects tested positive for syphilis;
- •Active or latent tuberculosis at screening (can be enrolled if appropriately treated);
- •Any of severe laboratory abnormalities in liver function, renal function, bone marrow function, coagulation function, pulmonary function, cardiac function at screening;
- •History of severe allergy or known hypersensitivity to any of the active ingredients of the drugs, excipients, or rodent-derived products, xenoproteins included in this trial, or subjects with allergic constitution;
- •Severe heart diseases;
- •Severe hepatobiliary disease;
- •Presence of medical conditions that are obviously unstable or not effectively treated;
- •Presence of uncontrollable bacterial, fungal, viral or other infections, requiring antibiotic therapy;
- •Have received live/attenuated vaccination within 4 weeks prior to screening or plan to receive live/attenuated vaccination throughout the study;
- •Have received any commercially available Janus kinase inhibitor or Bruton tyrosine kinase inhibitor within 3 half-lives prior to screening;
- •Have received B-cell targeted therapy prior to screening;
- •Have received a biologic agent other than B-cell targeted therapy within 5 half-lives prior to screening;
- •Previous received therapies with CAR-T cells or other genetically modified T cells;
- •Have received therapeutic dose of corticosteroids within 7 days prior to leukapheresis or within 72 hours prior to infusion;
- •Have received any other study drugs for SLE within 4 weeks prior to leukapheresis;
- •Subjects that have undergone major surgery within 4 weeks prior to lymph depletion or those who are scheduled to undergo major surgery during the study period, or whose surgical wounds have not fully healed prior to enrollment;
- •Subjects that have donated blood for ≥ 400mL or had significant blood loss equivalent to at least 400mL within 4 weeks prior to screening, or have received a blood transfusion within 8 weeks, or plan to donate blood during the study period;
- •History of ≥ grade 2 bleeding within 4 weeks prior to screening or need for long-term continuous anticoagulant therapy;
- •Subjects with severe mental illness;
- •Alcoholics or subjects with a history of drug abuse;
- •Female subjects who are pregnant or lactating, or intend to pursue pregnancy within 2 years after the cell infusion; male patients whose female sexual partners intend to conceive within 2 years after the cell infusion;
- •History of malignancy；
- •Patients that have contraindications to any of the study procedures or have other medical conditions that may expose them to unacceptable risk, in the judgment of the investigators and/or clinical criteria.
研究组 & 干预措施
Experimental Arm
Experimental
Participants will receive CD19 CAR-T cell intravenous infusion
干预措施: CD19 CAR-T cell infusion (Biological)
结局指标
主要结局
Safety and tolerability
时间窗: Within 2 years after CD19 CAR-T cell infusion
Safety and tolerability will be assessed by incidence and severity of adverse events (AEs) and serious AEs (SAEs). Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are graded by ASTCT criteria, other AEs are assessed by CTCAE V5.0 criteria
次要结局
- Proportion of subjects with SRI-4 response(Within 2 years after CD19 CAR-T cell infusion (day 14, day 28, month 3, month 6, month 9, month 12, month 18, month 24))
- Pharmacokinetics (PK)(Within 2 years after CD19 CAR-T cell infusion)
- Pharmacodynamics (PD)(Within 28 days after CD19 CAR-T cell infusion)
- Changes in the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) - Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score from baseline(Within 2 years after CD19 CAR-T cell infusion (day 14, day 28, month 3, month 6, month 9, month 12, month 18, month 24))
- Changes in the Physician Global Assessment (PGA) score from baseline(Within 2 years after CD19 CAR-T cell infusion (day 14, day 28, month 3, month 6, month 9, month 12, month 18, month 24))
- Changes in immunological indexes from baseline(Within 2 years after CD19 CAR-T cell infusion (day 14, day 28, month 3, month 6, month 9, month 12, month 18, month 24))
- Changes in level of anti-nuclear antibody (ANA) in peripheral blood from baseline(Within 2 years after CD19 CAR-T cell infusion (day 14, day 28, month 3, month 6, month 9, month 12, month 18, month 24))
- Changes in levels of complement C3 in peripheral blood from baseline(Within 2 years after CD19 CAR-T cell infusion (day 14, day 28, month 3, month 6, month 9, month 12, month 18, month 24))
- Changes in level of anti-double stranded DNA (dsDNA) antibody in peripheral blood from baseline(Within 2 years after CD19 CAR-T cell infusion (day 14, day 28, month 3, month 6, month 9, month 12, month 18, month 24))
- Changes in levels of complement C4 in peripheral blood from baseline(Within 2 years after CD19 CAR-T cell infusion (day 14, day 28, month 3, month 6, month 9, month 12, month 18, month 24))
- Changes in levels of Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) from baseline in patients with cutaneous lupus erythematosus(Within 2 years after CD19 CAR-T cell infusion (day 14, day 28, month 3, month 6, month 9, month 12, month 18, month 24))
研究者
Qiubai Li
M.D. & Ph.D., Professor
Wuhan Union Hospital, China
研究点 (1)
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